J. Org. Chem. 1981,46, 2465-2466 77153-05-0;2 1 ~77153-06-1; , 22b, 77153-07-2; 2 2 ~77153-08-3; , 22d, 77153-09-4; 23b, 77153-10-7;23c, 77153-11-8; 23d, 77153-12-9; 24a, 77153-13-0; 24b, 77153-14-1; 25, 77153-15-2; 26, 77153-16-3; 27, 77209-98-4; N-ethyl-o-toluamide, 57056-81-2; N-ethylacetamide, 625-50-3; N-ethylformamide, 627-45-2; acetamidine HC1, 124-42-5; propionamidine HCl, 3599-89-1;propionamidine, 39800-84-5;benzamidine HCl, 1670-14-0;benzoylbenzamidine, 16776-73-1;benzoylbenzamidine HC1,38063-74-0; acetylbenzamidine HCl, 38063-68-2; benzoylacetamidine HCl, 38063-70-6; benzoylpropionamidine HCl, 77153-17-4;N-octadecanoylpropionamidine HCl, 77153-18-5; 040toluoy1amino)propionamidine HCl, 77172-39-5; 8-amino-Nbenzoylpropionamide, 77153-19-6; N-acetylbenzamide, 1575-95-7; fl-(p-toluoylamino)propionamidineHC1, 20482-62-6; N-octanoyl-
2465
N'-ethylguanidine, 77153-20-9; 3-amino-N-acetylpropionamidine 2HC1, 77153-21-0; N-[3-[(tert-butoxycarbonyl)amino]-1,2,4-trimethyl-5-pyrroyl]propionamidine,77153-22-1; 3-[(tert-butoxycarbonyl)amino]-5-carboxy-l,2,4-trimethylpyrrole hydroxybenzotriazolide derivative, 77153-23-2;N-octadecanoylpropionimide,7715324-3; propionitrile, 107-12-0; 2-methyl-2-imidazoline, 534-26-9; Nacetyl-N'-ethylguanidine HC1, 77153-25-4; N-benzoyl-N'-ethylguanidine, 77153-26-5; 3-aminopropionitrile fumarate, 1119-28-4; 3-(benzoylamino)propionitrile,1131-83-5;dimethyl (tosy1imino)dithiocarbonate, 2651-15-2; 4-[ [ [(aminoiminomethyl)amino]acetyl]amino]-N-[5-[ [ (3-amino-3-iminopropyl)amino]carbonyl]1-methyl1H-pyrrol-3-yl]-l-methyl-1H-pyrrole-2-carboramide 2HC1, 1813322-7; ethylguanidine sulfate, 57989-90-9.
Thiocarbonyl Transfer Reagent Chemistry. 3. Selective Displacements with Formaldehyde Hydrazones and Other Nucleophiles' Charles Larsen* Department of General and Organic Chemistry, University of Copenhagen, H.C. Orsted Institute, Copenhagen, Denmark DK2100
David N. Harpp Department of Chemistry, McGill University, Montreal, Quebec, Canada H 3 A 2K6 Received October 14, 1980 Formaldehyde hydrazones react with l,l~-thiocarbonylbis(1,2,4-triazole)to effect C-thioacylation. The 1,2,4-triazole leaving group on these stable thioglyoxylic acid derivatives could in turn be displaced by hydrazones, sulfonohydrazides, thiosemicarbazides, and hydrazides.
As part of a study on the reaction of amines and hydrazines with thiocarbonyl transfer reagent 1 (giving 2 and 3, respectively), we wished to examine the analogous re-
[
S
C N ) C = S
1
"
R z N C N hbNJ
2
R S
I
I I F N RzNNCN 'N
Table I. Preparation of Hydrazones of Thioglyoxalyl-l,2,4-triazoles 5a %
compd
mp, "C yield
(I-C,H,),NN=CHCSTri b (5a)
106-107
(CH,),NN=CHCSTri (5b)
134-135
(C,H,CH,),NN=CHCSTri (5c)
108-109
3
action with other nucleophiles. We now report that formaldehyde hydrazones (4)react cleanly with 1 to effect C-thioacylation giving 5. The yields of these stable, novel derivatives of thioglyoxylic acid (CHOCSOH, 6) averaged nearly 80%. Clearly, 4 reacts through carbon via intermediate 7 to displace 1,2,4-triazoleas indicated in Scheme I. The reaction is somewhat analogous to an enamine acylation.2 We have, however, found no literature example of acylations of formaldehyde hydra zone^.^ The triazolyl leaving group in 1 appears to possess a unique reactivity in that when 4b and 4c were combined with 1,l'-thiocarbonylbisimidazole8, no reaction took place.5 Attempts to extend this reaction to other aldehyde hydrazones (e.g., acetaldehyde N,N-dimethylhydrazone (9)) failed; only starting materials were isolated. It was our (1) For Part 2 in this series, see: Larsen, C.; Harpp, D. N. J. Org. Chem. 1980,45, 3713. (2) House, H. 0. "Modern SyntheticReactions"; Breslow, R., Ed.; W. A. Benjamin: Menlo Park, CA 1972; pp 766-772. Reagent 1 has been shown to react with enamines.4 (3) Larsen, C., unpublished results. (4) One report has appeared concerningthe reaction of formaldehyde
hydrazones with acetic anhydride; however, the reactions were complex, and acylation did not take place on carbon. Lamberton,J. A.; Nelson, E. R; Triffett, A. C. K. Aust. J. Chem. 1974, 27, 1521. (5) Some of the special displacement reaction properties of reagent 1 have been published: h e n , C.; Steliou, K.; Harpp, D. W. J. Org. Chem. 1978, 43,337.
'H NMR, 6
50 1.38 (d, 1 2 H, CH,), 4.20 (sept, 2 H, CH), 8.02 (s, 1 H, triazole), 8.33 (s, 1 H, =CH), 9.27 (s, 1 H, triazole) 96 3.40 (s, 6 H, CH,), 8.13 (s, 1 H, triazole), 8.20 (s, 1 H. =CHL 9.33 (s. ., 1 H, tria'zole) 82 4.83 (s, 4 H, CH,), 7.33 (m, 1 0 H, C,H.). 8.00 (s. 1 H', t&zole), '8:33 (s, 1 H, =CH), 9.23 (s, 1 H, triazole)
Satisfactory analytical data (kO.3% for C, H, N) were reported for all compounds. Tri = l,2,4-triazoyl.
expectation that the acetaldehyde derivative 9 might react more slowly than 4b,but at this time we have no explanation regarding the complete lack of reactivity with reagent 1. As expected from previous 5a-c (see Table I for physical data) are easily transformed by various amines and hydrazines to the corresponding thioamides and thiohydrazides (10-13, Table 11). One reaction worthy of special note is that 5b in its reaction with phenylhydrazine gives 14. This product presumably arises by addition of a second molecule of phenylhydrazine to the C=N moiety followed by elimination of dimethylhydrazine. Finally, 1,2,4-triazoleis displaced from 5b and 5c on treatment with
0022-3263/81/1946-2465$01.25/00 1981 American Chemical Society
2466 J. Org. Chem., Vol. 46, No. 12, 1981
Larsen and Harpp
Table 11. Reactions of 5 with Various Nucleophilic Reagentsa compd mp, "C %yield 'H NMR, (CH,),NN=CHCSNHCH,C,H, ( 1 0 )
111-112
81
(CH,),NN=CHCSNHC,H, (11)
102-103
48
(CH,),NN=CHCSNHNH, (12)
165-166
72
(C,H,CH,),NN=CHCSNH, (13)
141-142
90
C,H,NHNHCSCH=NNHC,H, ( 1 4 ) b
128-130
79
(CH,),NN=CHCSNHN=C(C,H,),
203-204
66
(CH,),NN=CHCSNHNH0,SC6H4CH, (16)
156-157 dec
48
(CH,),NN=CHCSNHNHCSNHC,H, (17)
141-142
47
(CH,),NN=CHCSNHNHCOC,H, (18)
179-1 80
98
76-78
89
(15)
(i-C,H,),NN=CHCSNH, (19) a
Satisfactory analyses were reported for all compounds. Scheme I
-s
N
+
It
N
R2
S
5 a, R = (CH,),CH; b, R = CH,; c, R = C,H,CH, less nucleophilic compounds such as hydrazones, sulfonohydrazides, thiosemicarbazides, and hydrazides t o give 15-18, respectively (Table 11).
Experimental Section Conditions and equipment used for the physical measurements were those described previously.' N,N-Dimethylhydrazone of Thioglyoxalyl-l,2,4-triazole 5b. To a stirred solution of formaldehyde, N,N-dimethylhydrazone (0.01 mol, 0.72 g) in CC& (10 mL) was added a solution of 1 (0.01 mol, 1.8 g) in CHC13 (10 mL) dropwise over a 15-min period. After the addition was completed the stirring was continued for 1h. The crystelline material was collected, suspended in ethanol, and fiitered again to yield 1.75 g (96%)of red crystals which could be recrystallized from ethanol. The same procedure was used for the preparation of 5a and 5 c. General Procedure for Preparation of Compounds Listed in Table 11. With the exception of the Nfl-dimethylhydrazone of thioglyoxalic hydrazide, all the compounds could be prepared by adding the reagent to a hot solution of 5b or 5c in ethanol and
6
3.08 (s, 6 H, CH,), 5.03 (d, 2 H, CH,), 7.07 (s, 2 H, CH), 7.47 (s, 5 H, arom), 8.58 (br s, 1H, NH) 3.13 (s, 6 H, CH,), 7.05 (s, 1 H, CH), 7.65 (m, 5 H, arom), 10.03 (br s, 1 H, NH) 3.10 (s, 6 H, CH,), 4.77 (br s, 2 H, NH,), 7.00(s, 1 H, CH), 9.0 (br s, 1 H, NH) 4.70 (s, 4 H, CH,), 7.16 (s, 1H, CH), 7.38 (m, 1 0 H, arom), 8.03 (br s, 2 N,NH) 7.15 (m, 11 H, CH, arom), 8.08 (br s, 2 H, NH), 9.57 (br s, 1 H, NH) 2.,9 (s, 6 H, CH,), 6.95 (s, 1 H, CH), 7.67 (m, 1 0 H, arom), 11.17 (br s, 1 H, NH) 2.43 (s, 3 H, CH,), 3.15 (s, 6 H, NCH,), 6.8 (s, 1 H, CH), 7.62 (m, 4 H, arom), 8.9 (br s, 1H, NH), 9.73 (br s, 1 H, NH) 1.27 (t, 3 H, CH,), 3.13 (s, 6 H, CH,), 3.67 (m, 2 H, CH,), 6.9 (s, 1 H, CH), NH, baseline) 3.20 (s, 6 H, CH,), 7.0 (s, 1.H, CH), 7.87 (m, 5 H, arom), 10.75 (s, 1 H, NH, NH, baseline ) 1.23 (d, 6 H, CH,), 3.93 (h, 1 H, CH), 7.00 (s, 1 H, =CH), 7.92 (br s, 2 H, NH)
Low-resolution mass spectrum gave a parent ion at m / e 270. heating the solution to the boiling point for 1or 2 min (after which the red color had disappeared). After the mixture was cooled in ice-water the precipitated crystals could be collected. The products thus obtained were recrystallized from ethanol to give colorless or yellow crystals. In the case of the N,N-dimethylhydrazone of thioglyoxalichydrazide the reagents were mixed in the cold, as heating caused evolution of hydrogen sulfide, resulting in the formation of a gum. N,N'-Dibenzylhydrazone of Thioglyoxalyl-l,2,4-triazole 5c. To a stirred solution of formaldehydeN,N-dibenzylhydrazone (0.01 mol, 2.24 g) in CCll (15 mL) was added a solution of 1 (0.01 mol, 1.8g) in CH2Clz (10 mL) dropwise. The strongly red-colored solution was filtered to give 0.60 g of triazole. The filtrate was evaporated in vacuo to give a red oil which crystallized upon standing. Addition of ethanol and filtration gave 2.75 g of red crystals. Formaldehyde N,N'-Dibenzylhydrazone (4c)P To a stirred solution of N,N-dibenzylhydrazine (0.025 mol, 5.3 g) in methanol (15 mL) was added a solution of 37% formaldehyde in water (0.025 mol, 2.05 8). Ten minutes after addition was completed an exothermic reaction took place, and crystals separated. After 30 min the reaction mixture was cooled in ice-water and the crystals were filtered and dried (4.7 g), From the filtrate an additional 0.85 g was obtained by adding ca. 15 g of ice. Recrystallization from methanol gave 5.15 g (92%) colorless crystals with mp 47-47.5 "C. Anal. Calcd for CISHl6N2:C, 80.32; H, 7.19; N, 12.49. Found: C, 80.34; H, 7.14; N, 12.53.
Acknowledgment. We thank the Natural Sciences and Engineering Research Council of Canada and the Danish Natural Science Research Council for financial support of this work. Registry No. 1, 63976-76-1; 4a, 39837-46-2; 4b, 2035-89-4; 4c, 38663-41-1; Sa, 77060-54-9; 5b, 77060-55-0; 5c, 77060-56-1; 10, 77060-57-2; 11, 77060-58-3; 12, 77060-59-4; 13, 77060-60-7; 14, 77060-61-8; 15, 77060-62-9; 16, 77060-63-0; 17, 77060-64-1; 18, 77060-65-2; 19,77060-66-3;Nfl-dibenzylhydrazine,5802-60-8; formaldehyde, 50-00-0. (6) Norman, R. 0. C.; Purchase, R.; Thomas, C. B.; Aylward, J. B. J. Chem. SOC.,Perkins Trans. 1 1972, 1692.
